Altered emotional behavioral responses in mice lacking brain-type fatty acid-binding protein gene.

Brain-type fatty acid-binding protein (B-FABP) belongs to a family of intracellular lipid-binding proteins. B-FABP exhibits a binding affinity to long-chain fatty acids (FAs) whose effects on brain functions including development, emotion, learning and memory have been proposed. B-FABP is localized in the ventricular germinal cells in embryonic brain and astrocytes in developing and mature brain of rodents. In the present study we generated the mouse harboring a null mutation in the B-FABP gene and studied its phenotype. B-FABP mutant mice exhibited the enhanced anxiety and increased fear memory as well as the decreased content of docosahexaenoic acid (DHA) in their brain during the neonatal period without detection of any histological changes in the brain. In the adult brain, B-FABP was localized more numerously to the astrocytes in the amygdala and septal area than to those in the hippocampal area. Analysis of FA content in the amygdala of adult brain revealed that arachidonic and palmitic acids increased significantly in the mutant mice compared with wild-type. Furthermore, the response of N-methyl-d-aspartate receptor-mediated current to DHA in isolated neurons from B-FABP mutant brain was significantly decreased compared with that of wild-type, while no significant differences were detected in behavioral responses related to the spatial learning/memory or in the hippocampal long-term potentiation. These data indicate that B-FABP is crucially involved in the fear memory and anxiety through its binding with FAs and/or its own direct effects on pertinent metabolism/signaling of FAs.